On Health Watch News: Scrambler Therapy technology was cleared by the FDA in 2009
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality.
The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner.
To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive.
The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.
Chronic pain is estimated to affect 100 million people in the USA alone, resulting in up to $635 billion in medical expenses and lost productivity each year. It predisposes to psychiatric comorbidity, and its massive impact is highlighted by the fact that it is the most common cause of long-term disability in the USA.
In simplest terms, pain can be defined as a bodily sensation experienced during genuine, or perceived tissue injury. In the acute setting, this sensation can serve as a protective role by alerting an individual to avoid potentially harmful stimuli and to protect the body during healing. When pain fails to communicate biologically useful or accurate information, it is maladaptive and thereby becomes a disease state in its own right. It is generally agreed that pain becomes “chronic” when it persists beyond the expected period of tissue injury and healing. The specific duration of symptoms required to qualify for a diagnosis of chronic pain is debatable but generally is considered to be in the range of 3 to 6 months.
The perception of noxious stimuli originates from nociceptors of the peripheral nervous system. Nociceptors recognize stimuli in the form of thermal, mechanical, or chemical inputs. The stimulation leads to activation of primary sensory nerve fibers that transmit this information to the central nervous system, via a complex network of interneurons housed predominantly in the dorsal root ganglia, posterior horn of the spinal cord, brain stem, and thalamus. Ultimately, signals reach the forebrain for interpretation of the sensory experience. There are multiple mechanisms that underlie the dysregulation of this system in chronic pain. In the setting of injury, for example, inflammatory changes in the biochemical milieu surrounding peripheral nerves can result in hypersensitization of nociceptors, such that pain signals are communicated in the absence of appropriate stimuli. Neurons surrounding damaged tissue have even shown the ability to develop spontaneous discharges that communicate pain information in the absence of external input. Similarly, spinal cord neurons in the central nervous system exposed to repetitive pain stimuli may undergo changes that result in the transmission of action potentials with a reduced threshold of synaptic input.
Currently, several treatment modalities exist for the management of chronic pain, including physical therapy, pharmacologic therapy, behavioral medicine, neuromodulation, minimally-invasive interventions, and surgery. Unfortunately, the heterogeneous nature of chronic pain syndromes and the lack of a functional understanding of chronic pain contribute to the absence of a clearly identifiable, appropriate management strategy for many patients. Nonetheless, pharmacologic measures are commonly prescribed as a component of chronic pain management. With many medications available, such as non-steroidal anti-inflammatory agents, anticonvulsants, antidepressants, and opioids, it is exceedingly common for patients to use multiple agents to try to achieve reasonable pain control.
Recognizing the limitations and hazards of polypharmacy, increasing emphasis has been placed on the non-pharmacologic options for management of persistent pain. A strategy combining psychological and physical medicine approaches can provide significant benefit for many patients . Neuromodulatory techniques, particularly since the commercial availability of wearable transcutaneous electrical nerve stimulation (TENS) units in the mid-1970s, have gained popularity as an adjunct to both pharmacological and non-pharmacologic pain management. While promising in theory, the scientific data supporting such methods remain limited, without consistently-shown benefit, underscoring the need for novel therapeutic options.
The aim of this paper is to review what is known about the mechanism of a relatively new neuromodulatory approach, Scrambler Therapy, and discuss the trials and clinical experience, published to date, regarding its use.
Reports regarding Scrambler Therapy were identified by a combination of a database search, communication with investigators, and reviewing bibliographies of previously published manuscripts (Fig. 1). Several databases were utilized in the literature search, including PubMed/Medline, SCOPUS, EMBASE, and Google Scholar. Search terms including “Scrambler Therapy” and “Calmare” were used to identify all articles published prior to November 1, 2015. The search was refined with the use of Boolean terminology, specifically “Scrambler Therapy OR Calmare,” which yielded the largest number of articles. Results of these studies were reviewed and reported with an analytic intent that was primarily descriptive.
Giuseppe Marineo, a biophysicist who developed an interest in treating chronic pain, developed Scrambler Therapy and conducted basic and applied research related to its use. Marineo claims that chronic pain is the consequence of a phenomenon produced by the persistence in time of pain pathway activation, a typical condition of neuropathies. This process results in a loss of the linearity in the cause–effect relation that characterizes the physiological acute pain (which is protective) and creates a new type of nonlinear behavior of the pain system, that tends to self-sustain an anomalous response to painful and non-painful stimuli. Marineo proposes that the entire chronic pain process can be controlled by intervening on the afferent information aspects of pain, the variable that characterizes and mainly regulates every activity of the nervous system and represents its natural cybernetic expression. In short, Scrambler Therapy’s active principle is information control that manipulates the modulation or re-modulation of the pain system, and its physiological or pathological responses, in line with plastic properties of the nervous system. More specifically, a Scrambler Therapy unit is composed of five electrical stimulation channels that, through the surface receptors of C fibers, replace the endogenous pain information with a synthetic one of “non-pain” or “normal-self” that travels through the same pain pathways to the brain. Through plasticity within brain networks mediating the perception of pain, a series of treatments “retrain” the brain so that the area of concern is no longer considered painful. Marineo proposes that his functioning principle, like its neurophysiological target that uses receptors of C fibers, replaces the chronic pain information, rather than attempting to block its ascending path. An in-depth analysis of these differences are described in the International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317.
Scrambler Therapy has also drawn comparisons to spinal cord stimulation, which is another interventional technique that has been utilized in the treatment of refractory chronic pain. Spinal cord stimulation has been proven to be efficacious in a diverse array of pain syndromes, including refractory angina, failed back syndrome, and complex regional pain syndrome (CRPS), with the ability to reduce pain intensity in some cases by over 50 %. The drawback of this approach has largely been its invasiveness and cost.
Several authors of the present manuscript utilize Scrambler Therapy in clinical practice. Information in the following section is derived from their experience in treating hundreds of patients for a variety of pain syndromes. A patient treated with Scrambler Therapy has the area of pain identified and then has electrodes placed on the normal tissue around the painful site. The electrodes are not placed at the site of actual pain, but, instead, placed at a nearby location of preserved sensation. The dermatomal location is to feed this “non-pain” confusing information into the regular nervous circuit using peripheral nerves, rather than accessing the spinal cord. The intensity of stimulation is adjusted according to patient comfort and, if the placement is correct, the pain will usually be replaced by the Scrambler device sensation, which is often described as “pleasant, vibratory, and/or humming”. Up to the full set of five sets of electrodes can be used to treat the area(s) of pain. The device is allowed to run for a total of 30–45 min once the electrodes have been optimally positioned and stimulation intensity correctly regulated. After a session’s completion, patients may report a soothing sensation and note that the pain has been markedly reduced or has disappeared entirely.
The benefit from Scrambler Therapy, after the first treatment, generally lasts for a relatively short period of time. When treatment is reinitiated the next day, the same process happens, but the benefit generally lasts longer, e.g., for a few hours. In most cases, if the treatment has been given properly, with each treatment session, the non-pain (or meaningful relief) timeframe is extended. The duration of posttreatment relief classically lengthens with continued treatments until, ideally, the benefit is maintained throughout the entire day. Usually, Scrambler Therapy is given for a total of ten treatment sessions on consecutive weekdays, if feasible, although some patients need fewer and some patients need more treatments. Pain relief can be expected to persist for weeks to months after treatment is stopped. When patients relapse, booster sessions can be administered. It may only take one or two booster sessions to re-establish the benefit that previously occurred, and this benefit may last for a substantial period of time (oftentimes months or longer).
Scrambler Therapy is an operator-dependent methodology. Treatment success is highly dependent on the ability of the operator to eliminate pain during each single treatment without any significant patient discomfort. Failure to completely resolve pain in a treated area (or have a Visual Analog Score < =1) during each treatment session may lead to less satisfactory results. Experience has confirmed that more expert operators can eliminate pain during Scrambler Therapy when less experienced ones have failed. This may explain, in part, why data coming from different publications are relatively heterogeneous.
To date, 20 trials/reports of Scrambler Therapy are available for review (View Table). Eighteen have been published as manuscripts and two only as abstracts. One is a retrospective study, five deal with clinical practice experiences, 11 are prospective single-arm clinical trials, one is a randomized open-label controlled trial, and two are randomized, blinded, placebo-controlled trials.
View Table Here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973603/table/T1/?report=objectonly
The first trial was authored by the Scrambler Therapy developer, Marineo, in 2003 and reported the results of the treatment of 11 patients with cancer-associated, drug-resistant, visceral pain. This manuscript noted that pain was quickly and markedly reduced in the studied patients, with 9 of 11 patients stopping the use of pharmacologic pain therapy altogether after the first five sessions, without any associated side effects. Pain scores were reported to have decreased from approximately 8.5 out of 10, at study initiation, to approximately 0.5 out of 10, after 10 treatments. No adverse effects were reported.
A second trial was published in 2005, with Marineo as a co-author. A total of 226 patients with neuropathic pain were treated, including patients with failed back surgery, brachial plexus neuropathy, and other chronic pain conditions. This trial, while also uncontrolled, was impressively large and reported that 80 % of subjects had at least a 50 % pain reduction and 10 % experienced a reduction of 25–49 %. Ten percent (10 %) had no appreciable response. No adverse effects were reported.
Additional groups became involved in the clinical evaluation of this therapy with the publication in 2010 of the first study that did not include Marineo as a co-author. This was a pilot trial in 16 evaluable patients with chronic chemotherapy-induced peripheral neuropathy, conducted at Virginia Commonwealth University. The findings from this study were in line with the success seen with the previously reported trials. After ten treatments, the average reported pain score dropped nearly 60 %, with four patients achieving complete resolution of pain. Patients with recurrent pain successfully retreated with 1–3 subsequent treatments.
The next trial, currently only available as an abstract, involved ten patients with failed back surgery treated by an anesthesiology-trained pain physician. While it only noted a 28 % mean pain reduction, there were patients on this trial who had substantial relief after multiple other therapies had failed to provide benefit. The author of this abstract, a coauthor on the present manuscript, notes that there are three reasons why his success rate might have been relatively low: (1) he had limited operator experience; (2) he included study subjects with multifactorial intractable pain despite intensive polypharmacy; and (3) treatment while adjuvant anticonvulsants were continued. Empiric observations have suggested less than optimal outcomes if these medications are not discontinued prior to treatment.
Marineo and colleagues published the first randomized, controlled trial in 2011, which involved 52 patients with chronic neuropathic pain related to postsurgical causes, post-herpetic neuralgia, or spinal cord stenosis. Scrambler Therapy was compared to a control arm that utilized standard pharmacologic guideline-based recommendations, including frequent phone calls to modify analgesics. The pain reduction, after finishing 10 days of treatment, was 28 % in the control group (pain scores dropped from 8.0 to 5.8 out of 10) compared to a 91 % reduction with the Scrambler group (pain scores dropped from 8.1 to 0.7; p < 0.0001). Pain scores in the control arm were 5.7 and 5.9 at 2 and 3 months, respectively, as opposed to 1.4 and 2.0 in the Scrambler group (p < 0.0001). Analgesic consumption, including opioids, antidepressants, and anticonvulsants, decreased by 72 % in the Scrambler group. Allodynia also was reduced in the Scrambler patients, from 77 % at baseline to 15 % at 3 months. The benefit was obtained relatively equally amongst patients of all of the three diagnostic categories.
The sixth trial involved 82 (73 evaluable) prospectively-treated patients, about half of whom had cancer-related pain. Mean pain scores reduced from 6.2/10 before to 1.6/10 at the end of treatment and were 2.9/10 1 month after treatment was finished. Similar results were seen in patients with and without cancer. When patients were asked whether they would repeat this treatment, 97 % (71/73) responded affirmatively.
The seventh trial involved a cohort of eight patients treated with Scrambler Therapy for chronic low back pain. Patients were treated for six consecutive days; pain scores were recorded prior to initiation of treatment and after each session. The mean pain score was 8.12/10 at baseline, dropping to 6.93/10 after the first treatment. The mean pain score dropped to 3.63/10 in day 6. The group also recorded the Oswestry Disability Index (ODI) and found that mean score dropped from 49.88/100 to 18.44/100 by the end of the study, signifying an average drop from severe to minimal disability.
The eighth investigation was a prospective trial that reported on a series of 39 patients with cancer pain syndromes, including 33 with chemotherapy-induced peripheral neuropathy. Scrambler Therapy was associated with significant positive changes from baseline for a large number of outcomes, including degree of pain, interference with normal activities, and sensory neuropathy symptoms. The benefit persisted up to 3 months.
A small prospective trial published in 2013 involved 10 patients with post-herpetic neuralgia and included some data previously reported in another publication. The work reported a 95 % reduction in pain scores at 1 month, with sustained benefit observed at 2 and 3 month follow-up times.
In 2014, a prospective pilot trial experience was published, involving the treatment of 37 patients with chemotherapy-induced peripheral neuropathy, noting about a 50 % reduction in pain, tingling, and numbness. The increase in Scrambler benefit over the course of the trial suggested that, despite initial operator training in the administration of Scrambler Therapy, a learning curve was evident in this trial. The last 25 % of patients entered on this clinical trial did substantially better than did the first 25 % of patients, likely a reflection of improved technique afforded by greater experience.
The first attempt to compare Scrambler Therapy to a sham control was presented as an abstract at the 2013 Annual Meeting of the American Society of Clinical Oncology, involving 14 patients who were treated in a randomized, controlled, and double-blind manner. Results from this study have not been published as a manuscript. While the authors did note that the sham treatment from this particular trial was believable, in that the patients could not more often detect which of the two procedures was the true one, the authors did not observe any real improvements in neuropathy in the patients treated with the sham procedure versus Scrambler Therapy. This may well have been because this group had little experience with the technique prior to conducting their study. This finding fits with above-noted work that observed that there is a learning curve for the appropriate application of this therapy for treating chemotherapy neuropathy, which likely also applies to the treatment of other conditions. Additionally, the results of this trial support that there was not much of a placebo effect in this trial, as no benefit was noted in either trial arm. Paradoxically, this would support the argument that the positive results reported in other chemotherapy neuropathy Scrambler Therapy trials are not just ascribable to a placebo effect.
In 2015, a single-blind, sham-controlled, randomized clinical trial involving 30 patients with low back pain was reported from Virginia Commonwealth University. These authors noted significant decreases in the Brief Pain Inventory (BPI) back pain scores and pain interference scores (P ≤ 0.05). They also noted improvements in pain sensitivity, as measured by participants’ thresholds for pain in the initially painful area. Of note, the group randomizedtoScramblerTherapyhadsubstantialdecreasesin10 serum messenger RNAs (mRNAs) associated with nerve pain such as nerve growth factor (NGF) and glial derived nerve factor (GDNF), compared to no decreases in the sham group, understanding that these mRNAs have not yet been established as correlates for pain.
More recently, two subsequent single-arm prospective trials have been published which support therapeutic benefit. A pilot study was reported from an Italian hospital, evaluating outcomes of Scrambler Therapy in 25 patients with pain related to bony and visceral metastases. Each patient was scheduled for 10 daily sessions of treatment, and pain outcomes were measured by the use of a numeric pain scale. All patients were reported to have experienced at least a 50 % decrease in pain scores, with a mean pain score of 8.4 at baseline dropping to 2.9 after completion of the treatment course. The average duration of “pain control” (defined as >50 % reduction from baseline pain score) was 7.7 +/− 5.3 weeks. Sleep performance was also noted to improve significantly for the cohort. In Korea, Lee et al. performed an open-label, single-arm, exploratory study involving 20 patients with CIPN, metastatic bone pain, and postsurgical neuropathic pain. Pain scores decreased significantly, as did consumption of rescue opioid medication.
Two case series, published in 2013, each included three patients with cancer pain or post-herpetic pain. Both of these reports came from different authors and both reported positive benefits in the patients who were treated.
Sparadeo et al. reported their clinical practice experience regarding 91 of their initial 173 patients, representing all of those for whom they had collected data. These patients had a variety of pain syndromes, including CRPS, spine pain, neuralgias (such as post-herpetic or post-chemotherapy), and multi-focal pain problems. As part of their practice, with these 91 patients, they collected visual pain scores before and after each treatment for all of them and BPI questionnaires, in a subset of them, prior to treatment initiation and at 3- and 6-month follow-up times. The mean pain score prior to the first treatment was 7.2/10; it was 3.0/10 on the 10th day, prior to that day’s treatment. Relatively similar results were seen for the different pain syndromes. BPI scores at 3 to 6 months of follow-up were reported to be improved by more than 50 %.
In a second manuscript, Sparadeo and D’Amato analyzed the pre- and posttreatment data of 95 individuals (some of whom had been reported in the previous publication) entering their Scrambler Therapy program for treatment of chronic neuropathic pain, divided into two groups: CRPS and chronic spine-based pain. All patients were weaned from opioids and anticonvulsants being used for pain control. The data analysis revealed that 70 % of the entire sample was still reporting significant improvement 3 to 6 months following treatment. The two studied groups had similar levels of pain and degrees of lifestyle impact. Additionally, the 3–6-month successes were similar in the two treatment groups.
Another clinical practice experience report involved 147 patients treated at two United States military sites and one South Korean site. They noted that 38 % of patients had at least a 50 % pain reduction that lasted for more than a month.
Lastly, one retrospective report on Scrambler Therapy, involving 201 patients across multiple centers, was recently reported. Patients were treated for a variety of chronic pain syndromes; the most common indications included post-herpetic neuralgia, chronic low back pain, and polyneuropathy/ peripheral neuropathy. Patients were treated for a mean number of 10 sessions, with 39 patients experiencing complete resolution of pain symptoms sooner than this. The mean pain scores were 7.41 prior to treatment and 1.6 following treatment (P < 0.0001). Achieving a pain score of 0 during treatment was observed to associate with the durability of pain control, prompting the authors to advocate for a complete response as a target of therapy sessions.
Arguments against Scrambler Therapy certainly exist, with critics attributing much of the benefit to a placebo effect. Some of the positive endorsements in social media and on the Internet are only anecdotal. Additionally, the developer of Scrambler Therapy participated in the initial clinical trials, and this could be perceived as a potential conflict of interest even though it is scientifically desirable and logical to expect the device inventor to report the first set of results. Additionally, some of the reports claim that there is a phenomenal benefit that lasts for a long time, which sounds too good to be true. Lastly, there are no large, placebo-controlled, double-blinded clinical trials to estimate the effectiveness of Scrambler Therapy.
On the other hand, while some reports involved the inventor of the Scrambler device, these positive findings have been independently replicated by diverse groups in nearly all of the reported studies, involving over 900 patients in total. In some cases, the benefit achieved has been substantial, with some patients achieving complete pain resolution and substantially reduced dependence on pharmacologic therapy. There has been only one report of a negative experience. This was from one small, placebo-controlled trial in patients with chemotherapy-induced peripheral neuropathy. This was published only as an abstract, did not show much of a reduction in either study arm (arguing against a placebo effect), and was produced by a group that did not have much experience using Scrambler Therapy. This raises concerns regarding the validity of this trial, as data have supported that there is an extended learning curve with the provision of Scrambler Therapy, particularly for chemotherapy-induced neuropathy . At the same time, it must be noted that although this is the only negative trial published on Scrambler Therapy, the possibility of publication bias cannot be excluded. Negative experiences may not be put into publication form for various reasons, and so the currently available literature may be overestimating the positive experience with this technology.
The downsides of trying Scrambler Therapy for chronic pain primarily relate to the time and expense associated with its administration, in addition to noting that many proposed treatments for chronic pain have not withstood the rigors of time and/or well conducted randomized trials. Additionally, the therapy is not yet widely available and some insurance companies will not pay for it due to lack of evidence or will reimburse it at very low rates. However, some insurance companies are covering this treatment as they have started to note the benefit of this therapy in allowing patients to return to work, with decreased use of medications and procedures. Scrambler Therapy relies on practitioner skill and familiarity with technique, which can influence outcomes, as has been noted in the literature. This might impede rapid integration into practice, especially in the absence of formalized training.
Additional work is needed to better understand the mechanism of Scrambler Therapy and to conduct larger randomized clinical trials investigating the efficacy of Scrambler Therapy in a number of chronic pain states. A large, multi-center, randomized, sham-controlled double-blinded trial, involving patients with a variety of chronic pain syndromes, would strengthen the conclusions from initial studies. The data compiled, to date, support the feasibility and value of such an undertaking. Multiple other research lines of investigation would be helpful for further defining the worth of Scrambler Therapy. Such work could better evaluate the types of patients who benefit, the best means for teaching operators, and the compatibility of this approach with other treatment approaches. For example, as indicated above, there are recommendations to titrate down and discontinue anticonvulsant medications prescribed for pain management prior to initiating Scrambler Therapy, based on the theory and empiric clinical experience that these agents may interfere with the therapeutic mechanisms involved. Whether this is truly necessary could be a focus of future research. To better define the mechanisms of action, studies of brain reactivity (functional MRI) and peripheral nerve function (changes in epidermal nerve fiber density or electrophysiological measures or quantitative sensory nerve testing) would be useful.
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
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Minimizing the incidence of medication dependence in patients with chronic neuropathic pain (NP) poses significant difficulty for treating physicians. A recent increase in accidental deaths related to prescription opioid use has boosted the investigation of novel techniques for the treatment of chronic pain.1 In addition to the risk of opioid dependence, chronic pain patients suffer from a wide range of secondary medical conditions, including mental health difficulties and physical disabilities.2 Given the need for simultaneous treatment for chronic pain and associated comorbid conditions, pharmacological interventions alone are often inadequate when managing complex chronic NP syndromes.3
Scrambler therapy alleviates chronic pain relief with a novel, noninvasive stimulation. Photo credit: Edmond Boese, MD, Eagle, ID
Efforts to minimize risk of harm to chronic NP patients and their families prompted the development of noninvasive and nonpharmacological interventions.4 This trend toward more comprehensive and personalized standards of care will likely aid in appropriately relieving pain in patients suffering from NP syndromes, and will allow physicians to more directly address any associated medical conditions.
Among the novel alternative treatments for chronic NP syndromes is a patient-specific neurostimulative technique called scrambler therapy (ST). Scrambler therapy uses a noninvasive transcutaneous electrostimulation device that has shown promise for providers and patients seeking alternatives to traditional pharmacological pain relief techniques. Scrambler therapy works by introducing a pleasant sensation that acts as a distraction by sending a new message to nerve fibers that were used to receiving pain signals.
This retrospective review aims to shed light on the nature and extent of pain relief experienced during and across stimulation visits. The authors hypothesize that ST will reduce pain ratings for patients with a variety of chronic NP syndromes across and within stimulation visits.
Scrambler therapy was designed primarily as a method for treating cancer-related pain syndromes like chronic chemotherapy-induced peripheral neuropathy (CIPN).5Researchers explored the application of ST as a way of alleviating pain in cancer patients when metastases in the epidural space prevented use of nerve blocks and opioids from offering sufficient relief, and when adverse side effects prohibited achievement of adequate pain relief.
A preliminary case series reported findings of effective pain relief for 3 patients who were affected by severe cancer pain.6 In a separate pilot study of patients with CIPN, ST reduced pain scores by 53%, tingling by 44%, and numbness by 37%.7 This same study indicated that pain-relieving benefits of ST were sustained through 10 weeks of follow-up care. In another study, Coyne and colleagues measured changes in pain level on the Numerical Pain Rating Scale (NPRS)—a pain rating scale with 0 corresponding to “no pain” and 10 corresponding to “worst pain imaginable.” They found that when cancer patients were allowed to mark decimal points, pain ratings decreased from 6.6 before treatment to 4.6 over 3 months.8
Initial success in alleviating cancer-related NP syndromes allowed ST to emerge as a potentially successful treatment for a broader category of NP syndromes, including postherpetic neuralgia, low back pain, polyneuropathy, and peripheral neuropathy.4 Marineo et al aimed to directly compare ST to guideline-based drug therapy for patients grouped into a larger category of poly- or mono-radiculopathy.4 This randomized pilot study provided preliminary evidence that the neurostimulative technique may successfully alleviate pain better than pharmacology, reporting a mean rate of pain reduction of 91% in the first month of ST.4 As personalized noninvasive treatments develop, growing evidence has been presented in favor of these devices to successfully alleviate chronic pain over time.7,9
In a recent examination of ST, this method produced a reduction in chronic pain from a pretreatment score of 7.41 to 1.60 pain score (based on NPRS) following 10 sessions of treatment.9 This comprehensive study also divided patients into several broad categories of chronic pain, ultimately suggesting that the ST’s efficacy may be dependent on pain type. While promising, these pain rates and time frames for pain relief in patients with general chronic pain syndromes differed from those reported in the studies examining ST in a population of CIPN patients.7,8
Reports of inconsistent rates and time spans for achieving pain reduction reflected an urgent need for further research concerning the mechanism and efficacy of ST. Of particular interest to researchers was identifying the length of time necessary for ST to achieve consistent, maximal benefit. Additional considerations in pursuing this research included whether specific types of NP syndromes, pain locations, and severity levels were better suited to favorable treatment response with ST.
This retrospective review was conceived to bolster the current evidence basis by examining the efficacy of repeated ST treatments over time through a lens of specific NP conditions.
A retrospective chart review was conducted among 25 patients who received ST as administered by a neurologist between 2014 and 2015 at an outpatient pain management clinic in Hopewell, New Jersey.10 Basic demographic factors, including age and sex, were gathered. Pain-related data was also collected for pain diagnosis or classification, areas of pain, and descriptive characteristics of reported pain. Concomitant medications and pre- and post-stimulation blood pressure were noted.
Stimulation treatment details were gathered, including side effects, frequency (volume) of stimulation, location of treatment, dates of treatment, and number of treatments. Institutional review board approval was obtained for this chart review,10 which met compliance standards and ethical guidelines set by the participating institution.
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
New device offers relief
Chronic pain is a common problem that can take a significant toll on your mental and physical health. There arc various of causes of chronic pain, and a variety of strategies may be employed to manage pain or treat the cause.
These methods can be effective for some, particularly when combined into a comprehensive pain rehabilitation plan. However, it’s clear that addition-al therapy options are sorely needed.
Thankfully, one new therapy can be added to the list — at least for neuro-pathic pain tha€s caused by faulty nerve signals. Called scrambler therapy, it’s a novel form of electrical stimulation ap-plied to the skin. It involves sending scrambled electrical signals along nerve pathways to the brain in an attempt to retrain the brain to perceive the area of pain as normal, not painful.
Retrain the brain
With many types of chronic pain, normal nerve signals go haywire. There are multiple ways this can occur. Nerve endings may become damaged. Sensa-tions of pain may continue to be trans-mitted by nerve endings even after healing ofnearby tissues. Or nerve end-ings or nerves in the spinal cord may become somehow sensitized so that
even normal sensations —
such as
touch — cause the feeling of pain.
With the pain scrambler, the goal is to hijack the nerve pathways sending pain signals, and override the pain sig-nals with normal, nonpain signals. It’s believed that this can retrain the brain to recognize the area of pain as normal, not painful.
Wires from the pain scrambler machine run to electrode pads attached to points on the skin that are near, but not on, the site of pain. The scrambler electrodes are turned on, and the in-
tensity of the electrical signal is gradu-ally increased to where you can feel sensations, but not pain. The treatment continues for about 30 to 45 minutes. When successful, the pain is at some point replaced by the scrambler device sensation, which is Often described as a buzzing sensation. It’s believed that best results occur when the pain is com-pletely replaced by the buzzing sensa-lion during every scrambler session.
If the treatment is successful, the pain is usually greatly diminished or gone when the machine is shut off. This benefit may only last a few minutes to a few hours after the first session. But the process is repeated daily, and the post-treatment period Of benefit usu-ally gets longer after each session until the pain relief lasts for a day or more.
Ten sessions is the standard number needed, but it can be more or less than 10, depending on how things go.
Pain relief can persist for weeks to months after treatment is stopped. When pain returns, sometimes as few as one or two booster sessions can restore the benefit, and that benefit may last months or longer.
Mayo Clinic doctors are optimistic about the pain scrambler. Based on re-search and their own experience treating people at Mayo Clinic with the device,
it appears that the scrambler therapy can have good to sometimes dramatic results in people with select types of chronic pain who have reached the end of the line in terms of options. Importantly, it’s
generally well-tolerated.
The device appears to work best for chronic pain that is fairly isolated to one area, and due to faulty nerve signals, For example, research has shown good re-sults for conditions such as nerve pain (peripheral neuropathy) caused by che-motherapy, pain after a bout of shingles (postherpetic neuralgia), cancer-related pain, low back pain and numerous other pain syndromes.
It’s less clear if any benefit could be derived for Other common causes of chronic pain, such as osteoarthritis, fi-bromyalgia, irritable bowel syndrome or headache.
The downsides
Although the pain scrambler appears to reduce pain in most people, not everyone will benefit, and some people see only a modest benefit. In addition, i€s not widely available in the U.S.
Another potential downside is that it
(lakes a skilled operator for best resultsD that learning curve may skew research results or make it difficult for the device to be more widely adopted. -71
Scrambler therapy is a form of electrical stimulation applied to the skin for neuropathic pain that’s caused by faulty nerve signals.
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
In reality, NST is one of the 79th Medical Wing’s most cutting edge methods for managing chronic and debilitative nerve pain that impacts warfighters’ job performance and long-term quality of life.
“Like many civilians, military patients sometimes experience nerve pain after they’ve healed from injuries or have been treated for diseases,” said Lt. Col. Candy Wilson, 779th Medical Group nurse scientist and NST practitioner. “NST has proven to be a viable alternative to opioids for reducing or eliminating this kind of pain.”
Nerve pain that indicates no underlying injury or disease, technically known as peripheral neuropathic pain, can affect patients who undergo chemotherapy or suffer from diabetic or sciatica pain, drug/toxin exposure, infections stemming from surgical complications or incidents of trauma.
“A common case we treat with NST is a condition found among some wounded warriors known as phantom limb pain,” said Wilson.
Phantom limb pain is a condition in which an amputee experiences pain sensation from the part of the body that was removed.
Wilson and her nursing colleagues at the 779th MDG’s Acupuncture and Integrative Medicine Center administer NST using a Calmare machine. Calmare is the name of the manufacturer and it means “to soothe” in Italian.
NST involves sending a low voltage current of electrical stimulation through two electrode pads placed on the skin of the patient. One pad is placed on a part of the body inches away from the source of a nerve pain; the other pad is placed on a part of the body not affected by pain.
According to the Calmare Therapeutics Company’s official website, the stimulation scrambles the pain nerve signals to the brain. A “no pain” signal to the brain replaces a pain signal. Cleared by the Food and Drug Administration, the Calmare machine has been used successfully in Europe for the past 15 years and in the U.S. for the past few years. The website reports the treatment is painless, non-invasive and patients experience no adverse side effects.
“In effect, NST means we’re able to re-train the brain for reducing or eliminating pain,” Wilson said. “Recurring treatments over a certain amount of time result in prolonged pain relief for the patient.”
Patients needing treatment at Acupuncture and Integrative Medicine Center require a referral from their primary care provider. Then, their treatment is determined by one of the Acupuncture and Integrative Medicine Center’s physician acupuncturists.
“Referrals are necessary to ensure we are providing the appropriate and most effective treatment for our warfighters and other patient beneficiaries,” said 1st Lt. Folake Niniola, 779th MDG registered nurse. “Because of our thorough screening process, we’ve been very successful with this therapy and there have been no known or reported side effects or injuries from the use of this machine.”
Because of the Nerve Scrambler Therapy’s ability to reduce patients’ pain without side effects, the 79th MDW exemplifies the Zero Harm tenet of Air Force Medical Service’s patient care philosophy.
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
by Dr. Thomas Smith and Dr. Charles Loprinzi
The way we think of it, pain is about the most protective instinct and impulse known to humans! If you touch a hot plate, you retract your hand even before you actually feel the pain. Then, the pain comes – very localized – such that you can plunge the hand into cold water. After that, usually the pain goes away and you can then blame your son-in-law for leaving the hot plate on. But sometimes, the pain signal gets stuck in the “on” position, even though your hand has healed. There has been some damage to the nerve endings, and they are continuing to send the “pain” impulse when it is not doing you any good. The pain pathways in the spinal cord and the brain actually get bigger and more active; neurologists call this “wind-up.”
Pain has come to the attention of most oncologists because we CAUSE it with chemotherapy agents; we call it chemotherapy induced peripheral neuropathy (CIPN).
For the unfortunate 40-70% of chemo patients who get CIPN, it can range from being a nuisance to being life-destroying. Our patients describe constant burning or pins-and-needles pain, with numbness and tingling. It starts in the longest nerves that go to the hands and feet first, then progresses upstream. For many people it is just an inconvenience, and goes away in between chemo cycles and abates after treatment. But for others it persists, for years.
Preventing or treating CIPN has been frustrating. We both were part of the American Society of Clinical Oncology panel that made national clinical practice guidelines for CIPN. There are no drugs proven to prevent it, and alpha-lipoic acid, Vitamin A, natural products, L-carnitine – things that help in other neuropathies – were no better than placebo. Only one drug is proven to help, duloxetine (Cymbalta), with a reduction in pain of about 1 point on a 10 point scale.
Of course, there are other neuropathic pains that oncologists know all too well. The pain from a pinched nerve leaving a collapsed or damaged vertebra, shooting down the leg. The pain after shingles, “post-herpetic neuropathy” that can last for years. The pain after chest surgery, or mastectomy, or radiation.
Scrambler Therapy (marketed as Calmare™ therapy in the United States) is a new type of pain relief that uses a rapidly changing electrical impulse to send a “non-pain” signal along the same pain fibers that are sending the “pain” stimulus. We got interested in Scrambler Therapy because we thought it MIGHT help CIPN patients, and Scrambler Therapy appeared to be non-toxic. It had been cleared for safety by the FDA in 2009.
We were skeptical, but we did a trial of Scrambler Therapy. We treated 16 patients with refractory CIPN (present for at least 6 months, and refractory to medications); the group had a 60% reduction in their CIPN pain – in 10 days of treatment. Of the 16 patients we treated, essentially all reported some benefit, including 4 whose pain resolved to “0.” Function improved in most patients including less interference with walking and sleeping, for at least 3 months.
The setup is simple as shown in Figure 1 (Tom Smith’s legs). EKG electrodes are used to transmit the electrical impulses from a colored electrode to a black one, back and forth. The treatment is given for 30-45 minutes for up to 10 days in a row (excluding weekends). Our patients report a feeling like being bitten by electrical ants, or bee-stings. If the treatment is working, the sensation will change to a “hum” in the nerve and go to the ends of the nerve. We have to start above the painful area – remember, we are trying to replace the pain with a “non-pain” stimulus, and sometimes can work progressively down the legs and arms as pain relief occurs.
Figure 1: A typical setup to treat “stocking and glove neuropathy”
Colleagues at Mayo Clinic were skeptical and repeated the study in a larger group of people with CIPN. Pachman, Loprinzi and colleagues at Mayo reported about a 50% reduction in pain, numbness and tingling lasting at least 3 months. Of note, there appeared to be a learning curve, with the later patients getting better and longer lasting pain relief.
We will be the first to note that Scrambler Therapy lacks the “Good Housekeeping Seal of Approval” of cancer treatments – the well-designed, large, high statistical power, randomized controlled trial. We are both doing randomized trials, comparing Scrambler Therapy to “sham” (electrodes in the wrong place” and to TENS (trans-cutaneous electrical stimulation).
That said, we are interested in treatments that might work and don’t cause side effects. A recent review of at least 20 scientific reports noted no harm in any trial, with most reporting a substantial relief of pain. The two randomized trials comparing “sham” to real Scrambler Therapy showed a 50% reduction in low back pain, and a 91% reduction in pain from failed back syndrome, post herpetic neuropathy, and spinal cord stenosis. In all the trials, pain relief – if it happened – was obvious in the first 3 days, continued to get better, and usually lasted several months. There are additional reports of Scrambler Therapy having success in cancer somatic pain including bone and visceral metastases, complex regional pain syndrome, pediatric cancer chest wall pain, and others (see list below). The US Military has 17 Scrambler Therapy machines for treating both wounded warriors and civilians.
Some types of pain for which Scrambler Therapy has been used
Scrambler Therapy looks superficially likes TENS therapy. TENS applies similar electrodes on the skin and passes a pulse of electrical current between them. TENS is a completely different type of on-off current, and, classically, the effect wears off as soon as the electrodes are removed. When Scrambler Therapy works, it seems to reset or reboot the system for an extended period of time.
Spinal cord stimulation appears to have a same effect on pain that Scrambler Therapy appears to have. However, it involves putting electrodes on the spinal cord, and implantation of a pulse generator, similar to a pacemaker. It is also expensive – typically near $100,000 for a trial, then surgery and the equipment. It can last for years.
Quick answer, no, not very well yet. They are waiting for more traditional evidence (unlike the U S Military!) Some places are doing it for free on the clinical trials listed on clinicaltrials.gov. There is a list of certified centers on the Calmare website. An increasing number of insurers are paying for Scrambler if the person and their doctor appeals with lots of evidence from the trials above.
The machines themselves are expensive ($105,000 was the last quote we got) but can be used for a new person each hour, and last for years. The electrodes cost $4-15 dollars per person for a course of treatment. A person with training can do the treatment supervised by a physician with knowledge of the nervous system.
We have been using Scrambler Therapy routinely at our centers, and believe there is benefit to some patients. At the same time, we are humbled by the many therapies that have shown promise in phase II trials only to be no better than placebo or sham in Phase III trials. We need bigger randomized trials, sponsored by the NIH or someone who is not trying to sell the machines.
Dr. Thomas Smith is the Director of Palliative Medicine, Harry J. Duffey Family Professor of Palliative Medicine, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Dr. Charles Loprinzi is Regis Professor of Breast Cancer Research, Mayo Clinic
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com
Scrambler therapy is a pain management approach that uses a machine to block the transmission of pain signals by providing non-pain information to nerve fibers that have been receiving pain messages.
The first study on scrambler therapy was published in 2003 by a team of researchers led by Giuseppe Marineo, professor in delta research and development at University of Rome Tor Vergata in Italy. He and colleagues reported that scrambler therapy was effective at reducing pain symptoms in patients with severe, drug-resistant pain from terminal cancer.
Charles L. Loprinzi
The Calmare scrambler therapy device has since received FDA clearance in the United States for use in patients experiencing pain from cancer and chemotherapy, pain as a result of chronic diseases such as diabetes, multiple sclerosis and arthritis, back and neck pain, failed back surgery syndrome, and phantom limb pain among others.
HemOnc Today asked Charles L. Loprinzi, MD, Regis professor of breast cancer research at Mayo Clinic in Rochester, Minnesota, about the safety and efficacy of scrambler therapy, as well as his ongoing research efforts.
Question: Can you describe scrambler therapy and how it came about?
Answer: Scrambler therapy is an electro-cutaneous treatment. Although people may think of it as being similar to transcutaneous electrical nerve stimulation (TENS) therapy, scrambler therapy is felt to work through a different mechanism. TENS is thought to work through the gateway theory of pain relief, whereby normal touch sensations blocks pain sensations. Scrambler therapy, on the other hand, is proposed to provide normal-self, non-pain electrical information via nerves that have been transmitting chronic pain information. Through a process termed plasticity, this is able to retrain the brain so that it does not ascribe pain to the chronic pain area. Scrambler therapy consists of a machine, which looks somewhat like an electrocardiogram machine. Leads are placed on patients, around the areas of chronic pain. Scrambled electrical signals are then sent to the brain that perceives them as normal, non-pain signals. Via this process, the brain is retrained to think that there really is not pain in the area that is being treated.
Q: How and when did you become involved with this treatment approach?
A: I was introduced to scrambler therapy in 2010 by Thomas J. Smith, MD, now at Johns Hopkins University, who had heard about scrambler therapy and decided to try it in patients with chemotherapy-induced peripheral neuropathy (CIPN). He subsequently published a pilot trial that supported that scrambler therapy was an effective approach for treating established CIPN. After some internal debate as to whether I should look further into this treatment approach, which sounded quite strange to me, I did agree to study it. Having now treated more than 200 patients at Mayo, we published a paper on the use of this treatment for chemotherapy neuropathy, which concurred with Dr. Smith’s report, further supporting that this therapy was helpful for CIPN.
Q: What other published data support the value of scrambler therapy?
A: I am aware of 19 published reports regarding scrambler therapy, involving more than 800 patients. Seventeen of these are published manuscripts, whereas two are only published as meeting abstracts. These reports include clinical practice summaries, prospective non-randomized clinical trials and randomized controlled trials, including two trials that sought to double blind patients and investigators. The authors of 18 of the 19 reports concluded that scrambler therapy was a beneficial treatment approach, whereas one report — published only as a meeting abstract and only involving 14 patients — concluded that this was not an effective treatment. Of note, one relatively large randomized trial, with a non-blinded control arm consisting of optimizing medical management of pain, reported substantially more benefit from scrambler therapy than was observed in the control arm. Additionally, a relatively small placebo-controlled, patient-blinded trial reported a statistically significantly beneficial effect for scrambler therapy in a small number of patients with chronic low back pain. Thus, there are substantial data that support the value of scrambler therapy. Having said this, I readily admit that scrambler therapy has not yet been clearly proven to be beneficial. Ideally, additional randomized clinical trials will be reported to provide for more substantial clinical data regarding the true value of scrambler therapy. Dr. Smith is conducting one trial at Johns Hopkins and we, at Mayo, are gearing up for another one. This all takes time, energy and funds.
Q: Can you briefly discuss the findings from the clinical study you reported regarding the use of scrambler therapy in patients with established CIPN?
A: When we received the scrambler therapy machine, we decided to treat patients on a clinical trial as opposed to just using it for routine clinical practice. For this, we developed an open-label clinical trial to document our results and to learn how to provide this therapy. Prior to treating patients on this trial, we went to Rome for training. We then treated patients on this clinical trial, who had chronic pain or neuropathy with a pain and/or tingling score of at least 4 out of 10. In order to report data on a series of these patients, we took the first 37 patients who entered on this clinical trial who had CIPN as their designated clinical problem. We prospectively collected patient-reported outcome data on each of 10 days of treatment and then weekly for 10 weeks following that. Results, reported in Supportive Care in Cancer, illustrated that, during the treatment days, there was approximately a 50% reduction from baseline for pain, tingling and numbness scores. When we then followed the patients weekly, after the 10 days of therapy, the benefit, on the whole, persisted.
Q: Can you describe the treatment process and when beneficial results appear?
A: The area of pain/neuropathy is first defined and a set of leads is placed in normal sensation skin sites, close to the area of pain/neuropathy. The electrodes are then turned on with a gradual increase in intensity to a point where the patient is able to feel sensations, short of pain. When successful, the patient reports that the buzzing sensation has replaced an area of pain/neuropathy. This generally occurs within a minute or two. At times, electrodes need to be moved to obtain this sort of success. Sometimes, several sets of electrodes are needed to cover the area of discomfort. The scrambler machine stays on for about 30 minutes following successful electrode placements. The electricity is then turned off and the patient commonly reports that the pain/tingling is still markedly improved. After one treatment, the benefit is often relatively short-lived, lasting for minutes to hours. With repetitive days of treatment (standardly up to 10 treatments, although stopped earlier if the problem goes away completely and lasts overnight), the period of benefit increases until it lasts for a couple days. The benefit largely persists for weeks to months. Some patients relapse and can be successfully retreated, oftentimes only needing an additional few doses.
Q: Is this therapy routinely offered at Mayo Clinic?
A: Mayo recently began offering scrambler therapy as part of clinical practice. As with many new practice approaches, there are many questions that arise: How effective is the therapy? Who should be treated and for which conditions? How well is this approach covered by different insurance carriers? Admittedly, we do not have ideal answers for these and many other questions, but we are cautiously proceeding forward. There is considerable demand for scrambler therapy along with concerns that efficacy has not been proven and that the reported results from it sound too good to be true. But, these concerns are not too surprising, as there is often a wariness when a new therapy is initiated.
Q: Is this therapy routinely offered at places other than Mayo Clinic?
A: Yes, it is available at other select places. I understand there are more than 30 institutions in Italy and even more institutions in South Korea that provide scrambler therapy as a part of clinical practice. Multiple United States military institutions also offer scrambler therapy. In the United States, I estimate that there are between 15 and 30 sites that are actively offering this treatment. It should be noted that there is a learning curve in terms of making this therapy work. For example, in our paper where we looked at CIPN, even though we had reasonably good experience which included visiting the inventor in Rome and being trained by him, we did a whole lot better with the later patients we treated than we did the first 25% we treated.
Q: What type of feedback have you received on the therapy?
A: There are patient testimonials, which can be found on the Internet, whereby patients swear by this therapy. In line with this, I have seen some phenomenal results in patients. We have clinical trial data that asked patients, daily while they were receiving 2 weeks of outpatient therapy and then weekly for 10 weeks of follow-up, whether they would recommend this treatment to others. Approximately 80% of the replies noted that they would recommend it, 1% said that they would not and the rest said that they were unsure. There, admittedly, are some people who say this therapy did not work for them.
Q: How much of an issue is cost?
A: There are the issues regarding the cost of the machine, the cost of training and whether insurance companies cover this therapy. There are some insurance companies that cover the therapy, having realized that it is a lot cheaper than alternative therapies that might be employed for the same patient problem. This is certainly an evolving process. The cost can run anywhere between $200 and $500 per session, and up to 10 sessions may be recommended. This is less expensive than some other procedures and therapies employed for chronic pain, such as spinal cord stimulators. There are some patients who choose to pay for the treatments on their own, if not covered by insurance.
Q: Are there any side effects associated with this therapy? Do they outweigh the benefit, in your opinion?
A: There have not been many documented side effects with this therapy. People feel a buzzing sensation when the machine is working and sometimes this can be uncomfortable. If pain happens during the procedure, the signal intensity should be turned down and/or off. At times the electrode leads can be moved to an alternative site, sometimes by just a couple centimeters. Occasionally, patients may develop some skin irritation or bruising under the sites of the leads. There have been some patients who report more pain in the day or days following the treatment, but it is not apparent that this is more than the normal process of a waxing and waning of the baseline pain. Overall, the reports in the literature have been largely free of side effects.
Q: Is there anything else you would like to add?
A: Although if I consider myself to be a fairly conservative clinician and have not been shy about publishing negative results from many clinical trials, I do believe that scrambler therapy works. This contention is based on the knowledge that the majority of the reports in the literature are positive an also the personal experience I have observed in many patients, including seeing dramatic reductions of symptoms in some patients that did not derive similar benefit from previous treatment approaches. – by Jennifer Southall
If you would like to discuss what Carolina Pain Scrambler do to help relieve your chronic pain symptoms or receive more information on our treatment process, please do not hesitate to call us at 864-520-5011 or you can email us at info@carolinapainscrambler.com